Single-cell RNA sequencing reveals dynamic immune cell infiltration in mouse lungs during influenza A infection 4062

Abstract Description Understanding pulmonary pathogenesis during influenza infection is critical for developing effective therapies. We are investigating BALB/c mice infected with the PR8 strain of Influenza A virus at days 1, 3, and 6 post-infection. These time points were selected because viral content peaks at day 3 and returns to day 1 levels by day 6, during which mice experience nearly a 30% loss in body weight. Single-cell RNA sequencing of lungs from these mice is ongoing. In the meantime, reanalysis of a publicly available dataset has revealed dynamic changes in lung cellularity, characterized by significant infiltration of myeloid and lymphoid cells. Early recruitment of inflammatory monocytes (Ccr2, Ly6c2) was observed, followed by increased lymphocytes, including activated T and B cells, by day 3. In late infection, there was a shift towards increased tissue-resident macrophages (Cd11c, Siglec-F) and profibrotic macrophages (Spp1), indicating a transition from acute inflammation to fibrotic processes. Interferon pathways were activated, with elevated expression of genes such as Isg15, Irf7, and Oas1a. Pro-inflammatory cytokines (Cxcl10, Ccl5) also increased, indicating strong immune activation. These findings offer preliminary insights into lung immune responses during influenza infection. We aim to corroborate these results with our data and enhance understanding of pulmonary pathogenesis to inform targeted interventions against influenza-induced lung disease. Funding Sources Funding provided by Laboratory Directed Research and Development funds (24-ERD-025) to N.R.H. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-2001043. Topic Categories Computational and Systems Immunology (COMP)